In the United States in 2002, approximately 7.8 million women aged 50 and over had osteoporosis of the hip and an additional 21.8 million had low bone mass or osteopenia of the hip and were at risk for developing osteoporosis. Data, largely from cross-sectional studies, suggest that osteoporosis is associated with increased tooth loss, alveolar bone loss, and periodontal attachment loss. Oral health research studies investigating progression of periodontal disease and alveolar bone loss often involve multilevel, nested measures at the tooth-site level within subjects followed longitudinally over time. Disease processes may vary within a subject's mouth or over time within a subject and disease processes may differ between subjects. Typically, regression modeling approaches do not distinguish among effects of chronic or patient-level associations and associations with acute changes over time or spatial variation within a mouth. A better understanding of the multilevel disease processes could lead to more effective clinical follow-up procedures and more effective therapies. Our long-term goal is to slow the progression of alveolar bone loss and clinical attachment loss in post-menopausal osteopenic women with periodontitis. The specific aims of this proposal are to: 1) Develop computing macros, based on generalized estimating equation methodology, that can be implemented in SAS and R for fitting and statistically comparing separate within-mouth, across-time, and between-subject effects in correlated data regression models;2) Through simulation, develop guidelines for study design, including sample size, to ensure adequate power to detect different within-mouth, across-time, and between-subject effects;and 3) Apply the developed regression analysis methodology to existing data from our recently-completed National Institute of Dental and Craniofacial Research (NIDCR)-funded (R01DE012872) randomized double-blind, placebo-controlled clinical trial of sub-antimicrobial dose doxycycline (SDD) in postmenopausal osteopenic women with moderate to advanced periodontitis. The proposed analyses will utilize existing oral radiographic and clinical periodontal measures, as well as serum inflammatory biomarker and systemic bone mineral density measurements, from the 128 women who were enrolled in the 2-year clinical trial. The objectives of the secondary data analyses are to identify oral and systemic factors associated with alveolar bone loss and periodontitis progression over a 2-year period, distinguishing among effects of chronic or patient-level associations and associations with acute changes over time or spatial variation within a mouth. A better understanding of the complex, multilevel associations among oral and systemic factors associated with alveolar bone loss and periodontitis progression could lead to new clinical follow-up protocols and therapeutic approaches that will improve the oral health of this population. PUBLIC HEALTH RELEVANCE: Through the planned research project, statistical analysis and research design tools will be developed to investigate factors associated with oral disease processes that may vary within a given subject's mouth from tooth to tooth, over time as a subject ages or undergoes therapy, or between subjects with different characteristics. The methods will be used to identify oral and systemic factors associated with oral bone loss and periodontitis progression over a 2-year period among post-menopausal osteopenic women with moderate to advanced periodontitis. A better understanding of the oral disease processes could lead to more effective clinical follow-up procedures and more effective therapies in this type of population.